1. Field of The Invention
The present invention relates to a method for separating a blood material into blood component products. More particularly, the present invention is concerned with a method for separating a blood material into leukocyte-removed blood component products, which comprises providing a multiple blood bag system comprising a primary bag containing a blood material, a leukocyte-removing filter device comprising a flat casing, and at least one satellite bag, and centrifuging the blood material or a leukocyte-removed blood product obtained from the blood material, using a centrifuge cup having the multiple blood bag system accommodated therein, to thereby separate the blood material or leukocyte-removed blood product into blood components, wherein the centrifugation is performed with the filter device being held by a filter device holder having a substantially flat dimension, which extends in a direction perpendicular to an inner bottom floor of the centrifuge cup and is retained between blood bags of the multiple blood bag system or between a blood bag of the multiple blood bag system and an inner side wall of the centrifuge cup, and wherein the filter device holder has a recess and the filter device is received by the recess in a manner such that a flat surface of the flat casing of the filter device is perpendicular to the inner bottom floor of the centrifuge cup. By the method of the present invention, the filter device of the multiple blood bag system can be accommodated readily, fittedly and stably into a centrifuge cup together with the blood bags in a compact fashion without the need for using an adhesive tape, so that the accommodation of a multiple blood bag system into a centrifuge cup can be readily performed without any additional cumbersome operations. Further, since during the centrifugation, the flat filter device is stably retained in the centrifuge cup in a state received by the recess of the filter device holder extending in a direction perpendicular to the inner bottom floor of the centrifuge cup, the danger of damaging the filter device and the blood bags is extremely reduced or eliminated.
2. Discussion of Related Art
In recent years, in accordance with the progress of immunology and study of transfusion, it has become apparent that side effects of transfusion are caused by the leukocytes contained in a blood material used for transfusion. Side effects of transfusion include not only relatively mild side effects, such as headache, nausea, chilliness and nonhemolytic febrile transfusion reactions, but also serious side effects. With respect to the latter, particularly when a transfusion recipient has an immunopathy, transfusion is likely to cause serious side effects, such as graft versus host (GVH) reaction, in which transfused leukocytes attack the skin and internal organs of the recipient, infections by viruses present in the leukocytes, e.g., cytomegalovirus infection, and allosensitization. For effective prevention of such side effects of transfusion, it is now widely practiced to remove leukocytes from a blood material by means of a leukocyte-removing filter.
As filters for removing leukocytes from blood materials (such as whole blood, red cell concentrate, and platelet concentrate), various types of filters comprising a casing having an inlet for blood and an outlet for leukocyte-removed blood and, packed in the casing, a filter medium for removing leukocytes, have been put to practical use (see, for example, U.S. Pat. Nos. 4,701,267, 4,936,998, 4,880,548, 4,923,620, and 4,925,572).
Generally, it is difficult to connect a leukocyte-removing filter to a blood bag containing a collected blood material under aseptic conditions unless a special apparatus, such as an apparatus for aseptic connection, is used. Therefore, when a filter is connected to a blood bag containing a blood material without using a special apparatus for aseptic connection, there is a danger that the blood material is contaminated with microorganisms. Because of such a danger, it is usually required that a blood material for use in transfusion which has been treated for removing leukocytes under unsatisfactory conditions with respect to asepsis be used within 24 hours from the leukocyte-removing treatment. On the other hand, it has recently been reported that when the removal of leukocytes from a blood material is practiced under aseptic conditions immediately after the collection of the blood material from a donor, not only can the storage life of the leukocyte-removed blood material be prolonged, but also the damage to the red cells and platelets can be reduced. Accordingly, various systems containing a leukocyte-removing filter have been proposed for aseptically removing leukocytes from blood immediately after the collection of the blood (see, for example, U.S. Pat. No. 4,596,657).
As a system containing a leukocyte-removing filter, which can be used for aseptically removing leukocytes from blood immediately after the collection of the blood, U.S. Pat. No. 4,596,657 discloses a multiple blood bag system comprising a primary bag (as a blood collection bag), and a plurality of satellite bags, one of which is connected to the primary bag (blood collection bag) through a leukocyte-removing filter. The use of such a leukocyte-removing multiple blood bag system involves an operation in which blood is collected in the primary bag and the primary bag containing the blood is placed in a centrifuge cup together with the filter and the satellite bags, and the blood is subjected to centrifugation so as to be separated into a plasma layer (containing or not containing platelets depending on the centrifugation conditions) and a red cell concentrate layer.
Recently, a multiple blood bag system of the above-mentioned U.S. Pat. No. 4,596,657 has been introduced to the market, which employs as the filter a disk-like leukocyte-removing filter (disclosed in, for example, Unexamined Japanese Patent Application Laid-Open Specification Nos. 3-502094 and 1-249063) having a configuration and a cross-section shown in FIGS. 7(a) and 7(b), respectively. This disk-like filter employs a casing composed of a disk-like main body having a blood inlet and a blood outlet which protrude outwardly of the planes of both sides of the main body. However, actual experiments conducted using this commercially available multiple blood bag system, have revealed that it is very difficult to fittedly and stably accommodate the filter in a centrifuge cup together with the primary bag and the satellite bags. For example, when the filter is placed above the blood bags in the centrifuge cup as instructed in the manual accompanying the multiple blood bag system, the filter is unstable in the centrifuge cup, so that there is a danger that the filter is likely to be out of the centrifuge cup during centrifugation. For preventing the filter from being out of the centrifuge cup, it is necessary to fix the filter to the centrifuge cup together with the blood bags by means of an adhesive tape after the filter has been placed above the blood bags, thereby securing the entire multiple blood bag system to the centrifuge cup. This operation is extremely cumbersome. Further, even this operation cannot prevent the occurrence of damage to the filter and the blood bags due to the centrifugal force. On the other hand, when the filter is placed directly on the bottom of the centrifuge and under the blood bags, or the filter is placed between blood bags arranged one upon another, or the filter is placed between blood bags arranged side by side, it is difficult to compactly, fittedly and stably accommodate the entire multiple blood bag system in the centrifuge, leading to a danger that the filter and the bags are very likely to be destroyed due to the centrifugal force and the friction between the bags and the filter during centrifugation.
In order to solve the above problems, U.S. Pat. No. 5,100,564 discloses the use of a support means which is provided so as to engage the upper circumference of the centrifuge cup and which supports the filter thereon under the centrifugal force. In U.S. Pat. No. 5,100,564, when the multiple blood bag system is to be placed in a centrifuge cup, the blood bags are first placed in the centrifuge cup and then the support means is placed so as to engage the upper circumference of the centrifuge cup, and subsequently the filter is set on the support means. However, not only is the use of this support means cumbersome, but also the support means inevitably largely separates the filter means from the blood bags, so that it is impossible to attain compact accommodation of the multiple blood bag system in the centrifugal cup. Further, with this support means, there is a danger that the filter is inadvertently released from the support means and is out of the centrifuge cup together with circuit tubes during centrifugation, so that it is necessary to fix the filter to the support means by means of an adhesive tape or the like. Because of these problems, this technique has not been widely used.
With respect to the multiple blood bag system of U.S. Pat. No. 4,596,657 mentioned above, it is conceivable to incorporate therein a flat square filter as the filter instead of the disk-like filter employed therein. However, actual experiments conducted using a multiple blood bag system of U.S. Pat. No. 4,596,657 in which a flat square filter having a configuration and a cross-section shown, respectively, in FIGS. 8(a) and 8(b) is employed have revealed that there occur substantially the same problems as in the case of the above-mentioned multiple blood bag system of U.S. Pat. No. 4,596,657 employing a disk-like filter shown in FIGS. 7(a) and 7(b). Illustratively stated, when the flat square filter is placed above the blood bags in the centrifuge cup, the filter is unstable in the centrifuge cup, so that there is a danger that the filter is likely to be out of the centrifuge cup during centrifugation. For preventing the filter from being out of the centrifuge cup, it is necessary to fix the filter to the centrifuge cup together with the blood bags by means of an adhesive tape after the filter has been placed above the blood bags, thereby securing the entire system to the centrifuge cup. On the other hand, when the filter is placed directly on the bottom of the centrifuge and under the blood bags, or the filter is placed between blood bags arranged one upon another, or the filter is placed between blood bags arranged side by side, it is difficult to compactly, fittedly and stably accommodate the entire multiple blood bag system in the centrifuge, leading to a danger that the filter and the bags are likely to be destroyed due to the centrifugal force and the friction between the bags and the filter during centrifugation.
With respect to the above-mentioned flat square filter incorporated in the multiple blood bag system of U.S. Pat. No. 4,596,657, it is conceivable to modify the structure of the casing of the flat square filter so that the inlet and the outlet are located at the upper corners as shown in FIG. 9(a). When a filter having a configuration and a cross-section shown, respectively, in FIGS. 9(a) and 9(b) is placed between blood bags arranged side by side, it becomes less likely that the filter and the bags are destroyed due to the centrifugal force and the friction between the bags and the filter during centrifugation. However, the danger of damaging the filter device and the blood bags during centrifugation still remains. Since a leukocyte-removing multiple blood bag system is medical equipment, it is desired for the method of treating a blood material by use of the multiple blood bag system to be free of the danger of damaging the multiple blood bag system in the centrifugation operation.
In addition, generally, when a multiple blood bag system is accommodated in a centrifuge cup, the position of the filter in the centrifuge cup has conventionally been rather arbitrarily selected, and the danger of damaging the filter and the blood bags due to the centrifugal force is increased depending on the selected position of the filter. Therefore, it is desired to ensure that the filter is fittedly and stably accommodated at the most appropriate position in the centrifuge cup.